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Teenage lovers Jordan White and Amy Blue pick up a handsome drifter named Xavier Red while driving home from a club. Jordan gives Xavier the nickname "X". A late-night stop at a convenience store leaves the three on the run when X accidentally kills the store's owner, forcing the trio to hide in a motel to avoid arrest. While Jordan and Amy have sex in the bathtub, X learns from the local television news program that the store owner's wife disemboweled her children with a machete before committing suicide, thus, he concludes, removing any possibility of the trio being caught by the police.

Later that evening, Amy has sex with X, even though they do not get along. Eventually Jordan finds out, and things become tense as the two men develop a lingering sexual attraction for one another. As the trio journeys around the city of Los Angeles, they continue to get into violent situations due to people either claiming to be Amy's previous lovers or mistaking her for such. The FBI has a meeting and declares it will find Amy and kill her (exactly the same sentiment is voiced by several other parties in the film). She is mistakenly identified by a fast food window clerk as "Sunshine" and later by a character played by Parker Posey as "Kitten".

Jordan, Amy and X spend the night in an abandoned warehouse, where they engage in a threesome. While Amy goes to urinate, Jordan and X are attacked by a trio of neo-Nazis, one of whom had previously mistaken Amy for his ex-girlfriend "Bambi". The gang proceeds to beat up X and then hold Jordan down as the aforementioned neo-Nazi ties up and rapes Amy on top of an American flag. The group finally severs Jordan's penis with pruning shears and forces it into his mouth. After Amy breaks free, she kills the neo-Nazis with the shears and escapes with X, leaving Jordan for dead. The film ends with Amy and X driving aimlessly on the road with no communication as the film fades.

The Doom Generation received mixed reviews, with critics often comparing the film both favorably and unfavorably to Oliver Stone's Natural Born Killers. Film website Rotten Tomatoes, which compiles reviews from a wide range of critics, gives the film a score of 47% based on 34 reviews.[3]Roger Ebert famously gave the film "zero stars".[4] Ricky da Conceição of Sound on Sight named the film the best of Araki's "Teenage Apocalypse Trilogy" and said it "represented a major artistic leap forward" for Araki, who "creates a twisted pastiche of science fiction, nihilistic road movie and teen angst filtered with dead pan comedy and his own unique commentary on the depravity of modern America." He praised the set design, lighting, score and actress Rose McGowan, who "steals the show as the foul mouthed, morally aimless femme fatale on crystal meth and Diet Coke."[5]

In March 2012, the UK company Second Sight Films released a DVD with amamorphic widescreen and director/cast commentary.[6] Previous releases up until this point lacked the commentary, with many lacking the widescreen format.